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Home , Essential hypertension

Guidelines for Clinical Care Quality Department Ambulatory

Hypertension Guideline Team Essential

Team lead Patient population: Adults age 18 and older. Masahito Jimbo, MD Family Medicine Objectives: (1) Accurately diagnose hypertension. (2) Improve (BP) control. (3) Decrease hypertension-related morbidity and mortality. (4) Encourage patient’s self-involvement. Team members (5) Provide appropriate education and follow-up. (6) Provide cost-effective care. Michael P Dorsch, PharmD Pharmacy Key aspects and recommendations:

Mark W Ealovega, MD . Diagnosis General Medicine • Although a single, carefully taken blood pressure (BP) reading may predict future cardiovascular risk, for clinical purposes this risk is better identified by taking the mean BP level from recordings over R Van Harrison, PhD several visits. Medical Education • Home or ambulatory blood pressure monitoring helps improve BP control and identifies “white coat” Kenneth A Jamerson, MD and “masked” hypertension [IIA]*. Cardiovascular Medicine • If home BP monitoring is used, be sure the BP monitor is carefully calibrated. Educate patients on

proper technique.

• If mean BP > 135/80, screen for [IB]. Initial Release • National and international guidelines vary on how they define hypertension. Continue to classify office February 1997 BP readings consistent with JNC 7 (Table 4), until there is greater consensus regarding the new Most Recent Major Update definitions proposed by the 2017 ACC/AHA guidelines. May 2014 . Treatment Interim/Minor Revision • Incorporate patient’s risks and values using shared decision-making to tailor BP management [ID]. July 2019 • Blood pressure treatment targets for adults of any age:

- Without risk: < 140/90 mm Hg with no clinical risk: no clinical atherosclerotic cardiovascular Ambulatory Clinical disease (ASCVD), 10-year ASCVD risk score < 10%, and no chronic kidney disease (CKD), [IA]. Guidelines Oversight (Note: diabetes is already considered in calculating ASCVD risk.) Karl T Rew, MD - With ASCVD, ASCVD risk > 10%, or CKD: R Van Harrison, PhD - <130/80 mm Hg if without risk for hypotension (eg, without: orthostatic , failure, older age). (SBP of < 130 mm Hg ([IA] for ASCVD; DBP < 80 mm Hg [IA].) - Consider <140/90 mm Hg if risk for hypotension

Literature search service • Additionally, for CKD stages 3b-5, monitor more frequently due to increased risk for hyperkalemia. Taubman Health Sciences • Treatment of SBP over 160 mm Hg is important in reducing CVA and CHF risk [IA]. Library • Lifestyle modifications (eg, weight management, diet and restrictions, physical activity, alcohol moderation, tobacco avoidance) are important initial treatment steps to lower BP [IA].

• Begin drug therapy with a thiazide diuretic, ACE inhibitor, ARB, or long-acting dihydropyridine calcium channel blocker for almost all patients. Add second and third agents as needed to achieve For more information effective BP reduction goals [IA]. 734-936-9771 - Specific illnesses may guide the initial and subsequent choice of agents, eg: - ACE inhibitors (ARB for those unable to tolerate ACE inhibitors) for patients with renal disease, diabetes with either micro- or macroalbuminuria, or left ventricular (LV) dysfunction - Beta-blockers for those with CAD or CHF. © Regents of the University of Michigan • Over 70% of individuals require two or more drugs to achieve BP goals. A fixed combination therapy These guidelines should not be may be cost-effective. Once a day medications increase compliance and are preferred. construed as including all proper methods of care or excluding * Strength of recommendation: other acceptable methods of care I= generally should be performed; II = may be reasonable to perform; III = generally should not be performed. reasonably directed to obtaining Levels of evidence for the most significant recommendations the same results. The ultimate A = randomized controlled trials; B=controlled trials, no randomization; C=observational trials; D=opinion of expert panel judgment regarding any specific clinical procedure or treatment must be made by the physician in Clinical Background light of the circumstances presented by the patient. Incidence Forty-three million United States adults have hypertensive patients are adequately controlled. hypertension, representing 24% of the U.S. adult Uncontrolled hypertension results in end stage population; 20 million have no medication organ damage, which leads to significant mortality prescribed, and 12 million are on medication but and morbidity. not controlled. Thus, about one out of four (continued on page 6) 1

Table 1. Selection of Initial and Subsequent Antihypertensive Drug(s) Based on Concurrent Disease States Coexisting Disease Specific Agent* Relatively Contra- Comments Condition indicated Agents** Cardiovascular Angina  blocker; ACEI if LV Short-acting DHP CCBs are relatively dysfunction contraindicated for all coronary disease. MI History  blocker, ACEI CHF – Systolic ACEI, β blocker; ARB if Non-DHP CCB, HYD and nitrate if ACEI and ARB not tolerated ACEI not tolerated, alpha blocker  blockers should be used in very low dosages inhibitor and slowly titrated. Cardiomyopathy  blocker, non-DHP CCB diuretic, ACEI & ARB, (Hypertrophic) 1 blocker, DHP CCB Tachycardia (Supra-  blocker, non-DHP CCB ventricular) Bradycardia/heart  blocker, Non-DHP block CCB, 2 agonist Aortic/Mitral ACEI, DHP CCB, ARB if Regurgitation ACEI not tolerated Metabolic Diabetes ACEI, ARB Concerns that thiazide diuretics and  blockers may worsen control and  blockers may mask hypoglycemia have largely been refuted as clinically insignificant Gout losartan is uricosuric Diuretic-induced hyperuricemia does not require treatment in absence of gout or stones. Even with these, diuretics may be restarted if uric acid is controlled to < 6 mg/dl with allopurinol. Renal Disease Chronic Renal ACEI, ARB if ACEI not DHP CCB (alone) Avoid potassium-sparing agents due to increased tolerated risk of hyperkalemia. Loop diuretics preferred if creatinine is ≥ 2.5 (GFR < 30 ml/min). GU Impotence ACEI (ARB if ACEI not tolerated), DHP CCB Bilateral (or  blocker, DHP CCB ACEI and ARB equivalent) Renal Artery Pulmonary Reactive Airway  blockers should be started at low dose and Diseases slowly titrated. Psychiatric/CNS Headaches  blocker, non-DHP CCB Verapamil (not diltiazem) useful for cluster (Vascular) headaches and, to lesser extent, migraines. Pregnancy methyldopa,  blocker (except atenolol, propranolol ACEI and ARB are absolutely contraindicated. atenolol and propranolol), ACEI, ARB calcium channel blocker, labetalol, Drug Interactions Cyclosporine HTN  blocker, DHP CCB Lithium Usage  blocker, DHP Diuretics, ACEI and Thiazides may increase level by 25-40%. CCB, Non-DHP CB ARB Potassium sparing diuretics have minor effects.

* Antihypertensive Drug Classes Abbreviations Antihypertensive Drug Classes (cont.) Abbreviations ** May still be used Alpha 1 blocker 1 blocker Direct vasodilator NA under certain converting inhibitor ACEI Diuretic NA circumstances Angiotensin II ARB Hydralazine HYD Beta blocker  blocker Isosorbide dinitrate ISDN Centrally acting alpha-2 agonist NA Non-dihydropyridine calcium channel Non-DHP CCB Dihydropyridine calcium channel blocker DHP CCB blocker (eg-diltiazem, verapamil). (eg, , felodipine)

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Table 2. Antihypertensive Medications: Common Doses and Costs

30 Day Cost* Drug Class (generic name) Brand Name Usual Dosage Regimens Generic Brand Thiazide Diuretics hydrochlorothiazide generic 12.5mg.daily 25mg daily 50 mg daily $5-7 n/a chlorthalidone generic 25 mg daily $19 n/a Potassium Sparing/Thiazide Combination Diuretics amiloride /HCTZ** generic 5 mg/50 mg daily $19 n/a triamterene/HCTZ Dyazide 37.5 mg/25 mg daily $9 $70 /HCTZ Aldactazide 25 mg/25 mg daily $35 $85 ACE Inhibitors captopril Capoten 12.5 mg 2x/day 25 mg 2x/day 50 mg 3x/day $44-109 $93-235 benazepril Lotensin 5 mg daily 10 mg daily 20 mg daily 40 mg daily $6-7 $29 all quinapril Accupril 10 mg daily 20 mg daily 40 mg daily $9-20 $157 all lisinopril Prinivil/Zestril 5 mg daily 10 mg daily 20 mg daily 40 mg daily $4-5 $26-43 enalapril Vasotec 2.5 mg daily 5 mg daily 10 mg daily 10 mg 2x/day $13-20 $12-40 fosinopril Monopril 10 mg daily 20 mg daily 40 mg daily $9 all $32 all trandolapril Mavik 1 mg daily 2 mg daily 4 mg daily $11-15 $34 all moexipril Univasc 7.5 mg daily 15 mg daily $30 all $38-40 ramipril Altace 2.5 mg daily 5 mg daily 10 mg daily $6 all $193-237 perindopril Aceon 4 mg daily 8 mg daily $20-22 $62-76 ACE Inhibitor / Diuretic Combinations benazepril/HCTZ Lotensin HCT 5 mg/6.25 mg daily 10 mg/12.5 mg daily 20 mg/12.5mg daily $23-52 $56 all lisinopril/HCTZ Prinzide/Zestoretic 10 mg/12.5 mg daily 20 mg/12.5 mg daily 20 mg/25 mg daily $5 all $30-33 fosinopril/HCTZ Monopril HCT 10 mg/12.5 mg daily 20 mg/12.5 mg daily $38 all $83 all quinapril/HCTZ Accuretic 10 mg/12.5 mg daily 20 mg/12.5 mg daily 20 mg/25 mg daily $22-25 $153 all (continues on next page)

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Table 2. Antihypertensive Medications: Common Doses and Costs, continued Drug Class 30 Day Cost* Brand Name Usual Dosage Regimens (generic name) Generic Brand Angiotensin Receptor Blockers telmisartan Micardis 40 mg daily 80 mg daily $18 all $233 all olmesartan Benicar 20 mg daily 40 mg daily $15-16 $238-330 valsartan Diovan 80 mg daily 160 mg daily 320 mg daily $13-19 $254-346 irbesartan Avapro 150 mg daily 300 mg daily $10-13 $194-234 candesartan Atacand 8 mg daily 16 mg daily 32 mg daily $53 all $216-294 eprosartan Teveten 400 mg daily 600 mg daily $95 $95 losartan Cozaar 50 mg daily 100 mg daily 50 mg 2x/day $6-9 $163-240 azilsartan Edarbi 40 mg daily 80 mg daily n/a $202-220 Angiotensin Receptor Blocker / Diuretic Combinations valsartan/HCTZ Diovan HCT 80 mg/12.5 mg daily 160 mg/12.5 mg daily $10 $225-286 telmisartan/HCTZ Micardis HCT 40 mg/12.5 mg daily 80 mg/12.5 mg daily 80 mg/25 mg daily $53 $233 candesartan/HCTZ Atacand HCT 16 mg/12.5 mg daily 32 mg/12.5 mg daily $92-104 $243-264 losartan/HCTZ Hyzaar 50 mg/12.5 mg daily 100 mg/25 mg daily $8 $25-181 olmesartan/HCTZ Benicar HCT 20 mg/12.5 mg daily 40 mg/12.5 mg daily 40 mg/25 mg daily $106 $330 eprosartan/HCTZ Teveten HCT 600 mg/12.5 mg daily 600 mg/25 mg daily n/a $152 azilsartan/CTD Edarbyclor 40 mg/ 12.5mg daily 40 mg/12.5mg daily n/a $207 Calcium Channel Blockers Non-DHP verapamil SR Calan SR 240 mg daily $10 $287 diltiazem Cardizem 30 mg 4x/day 60 mg 3x/day 60 mg 4x/day 90 mg 3x/day n/a $322-378 diltiazem CD Cardizem 120 mg daily 180 mg daily 240 mg daily 300 mg daily $16-23 $1017-1805 DHP (dihydropyridines) amlodipine Norvasc 5 mg daily 10 mg daily $6 $50-65 felodipine Plendil 5 mg daily 10 mg daily $9-10 $43-100 nifedipine CC Adalat CC 30 mg daily 60 mg daily 90 mg daily $18 $103-120 Procardia XL nisoldipine Sular 20 mg daily 30 mg daily 40 mg daily $450 $484 isradipine CR Dynacirc CR 5 mg daily 10 mg daily $50-96 $54-108 (continues on next page)

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Table 2. Antihypertensive Medications: Common Doses and Costs, continued Drug Class 30 Day Cost* Brand Name Usual Dosage Regimens (generic name) Generic Brand Calcium Channel Blocker / ACE Inhibitor Combinations amlodipine/benazepril Lotrel 2.5mg/10mg daily 5mg/10mg daily 5mg/20mg daily $12-13 $73-78 trandolapril/verapamil Tarka 1mg/240mg 2mg/180mg 2mg/240mg 4mg/240m all daily $130 all $194 all Aldosterone Antagonists spironolactone Aldactone 25 mg daily 50 mg daily $6-10 $82-144 eplerenone Inspra 50 mg daily 50 mg 2x/day $56-110 $117-234 Beta Blockers atenolol Tenormin 25 mg daily 50 mg daily 100 mg daily $6-7 $22-40 propranolol Inderal LA 60 mg daily 80 mg daily 120 mg daily $22-35 $815 all Inderal XL labetalol Trandate/Normodyne 100 mg 2x/dy 200 mg 2x/day 300 mg 2x/day $20-24 $56-108 nadolol Corgard 40 mg daily 80 mg daily 160 mg daily $43-121 $163-450 metoprolol tartrate Lopressor 50 mg 2x/day 100 mg 2x/day $7 $94-124 metoprolol succinate Toprol XL 100 mg daily 200 mg daily $10-23 $62-96 Bystolic 2.5 mg daily 10-20 mg daily 40 mg daily $155-309 nebivolol Coreg 3.125 mg 2x/day 12.5-25 mg 2x/day 25 mg 2x/day $8-9 $57 all carvedilol Coreg CR 10 mg daily 20 mg daily 40 mg daily 80 mg daily $217 $280 Direct Vasodilators hydralazine generic 25 mg 3x/day 50 mg 3x/day 100 mg 3x/day $12-19 n/a minoxidil generic 5 mg 2x/day 20 mg 2x/day $26-48 n/a Centrally-acting alpha-2 agonists clonidine Catapres 0.1 mg 3xday 0.3 mg 3x/day $9-10 $264-507 methyldopa generic 25 mg 3x/day 500 mg 3x/day 1000 mg 3x/day $89 n/a Alpha Blockers doxazosin Cardura 1 mg daily 2 mg daily 4 mg daily $10-12 $150-158 terazosin Hytrin 1 mg daily 2 mg daily 5 mg daily $8 all $43 all prazosin Minipress 1 mg 2x/day 2 mg 2x/day 5 mg 2x/day $38-56 $142-337 Inhibitors Tekturna 150 mg daily 300 mg daily $192-258 $207-320 Other Diuretics torsemide Demadex 5 mg daily 10 mg daily $10-12 $17-19 (Furosemide –generic or Lasix – has no blood pressure indication, only volume control.) * Pricing information for brand drugs, Average Wholesale Price minus 10%. AWP from Lexicomp Online 07/2019. For generic drugs, Maximum Allowable Cost plus $3 from BCBS of Michigan MAC List, 07/2019. ** HCTZ = hydrochlorothiazide, CTD = chlorthalidone

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Table 3. Errors in Measurement of Blood Pressure

Faulty Technique Patient Related No effect on BP readings • Back not supported • Pseudo-hypertension • Menstrual phase • Arm not supported • Atrial fibrillation • Chronic caffeine ingestion • Elbow too high • Pain or anxiety • Phenylephrine nasal spray • Elbow too low • Acute smoking • Cuff self-inflation • Missed auscultatory • Acute caffeine (< 30 min.) • Examinee and examiner discordance in sex or • Feet not on ground • Acute ethanol (< 2 hours) race • Talking during BP reading • Bell vs diaphragm of stethoscope Faulty BP Equipment • Room temperature • Gauge inaccurate • Thin shirtsleeve under cuff (growing evidence, • Cuff not correct size not universally endorsed)

Table 4. Classification of Office BP Readings (JNC 7)

Category Systolic Diastolic Normal < 120 and < 80 Prehypertension 120-139 or 80-89 Hypertension • Stage 1 140-159 or 90-99 • Stage 2 ≥ 160 or ≥ 100

Table 5. Reversible Causes of Sustained Elevated Blood Pressure Readings

Medications: Medications (continued): Lifestyle factors Diet • NSAIDs * • appetite suppressants • alcohol > 2 drinks/day • High sodium (esp. elderly or • oral contraceptive agents • antidepressants • sedentary lifestyle African-American) • glucocorticoid or • MAO inhibitors Illicit drugs Associated Conditions mineralocorticoid steroids • cyclosporine • cocaine • • erythropoietin • amphetamines * interferes with antihypertensive medications • anabolic steroids

Rationale for Recommendations

Recommendations are organized under headings for: choice of which arm does not matter if at the initial • Diagnosis of hypertension measurement there are no differences between blood • Initial evaluation of newly diagnosed patient pressures taken on both sides. Caffeine, exercise, and • Treatment of hypertension smoking should be avoided for at least 30 minutes prior to • Monitoring blood pressure control measurement. (See Appendix for detail about devices and proper technique.) Patients should be informed of the Diagnosis of Hypertension readings, interpretation and necessary follow-up if indicated. If available, automated office BP measurement is preferred Performing BP measurement. BP readings need to be to non-automated BP measurement in the office. Elevated performed accurately to provide useful information. BP in BP in the office should be confirmed with home BP the office should be checked after 5 minutes of sitting quietly measurement, which is described in more detail below. in a chair, with feet on the floor, and arm supported at the heart level, and the results recorded on the medical record. Although a single, carefully taken BP reading may predict Standardizing the use of the same arm by all staff can future cardiovascular risk, risk is better identified by taking facilitate comparisons for sequential measurement. The the mean BP level from recordings over several visits. 6 UMHS Hypertension Guideline, July 2019

WCH. Documentation of WCH results in decreased drug Frequency of BP screening. Frequency depends on patient cost, with no change in LV mass, cardiovascular risk status regarding hypertension. outcomes, or well-being. WCH may carry a higher long • If BP is normal (< 120/80), measure BP at least annually term risk of hypertension, but at least one study has not (current expert opinion). Consider BP measurement at shown an increase in risk. every visit. • Masked hypertension refers to patients with target BP at • If BP is in the range (120-139 / 80-89 mm clinic, but elevated home BP. This condition may be nearly Hg), measure BP every 6 months. as common as WCH. These patients may have LVH or • If the BP average is ≥ 140/90, consider assessing for and other target organ damage despite normal office BP. Both correcting reversible causes of hypertension (Table 5). HBPM and ABPM can help identify masked hypertension, Aortic regurgitation may be a cause of isolated systolic resulting in more aggressive medication regimens and hypertension. improved cardiovascular outcomes.

HTN classification and follow-up assessment. National Currently, reimbursement for ABPM by Medicare is covered and international guidelines vary in how they define only for suspected WHC, defined by 3 or more office visit hypertension. Continue to classify the average initial BP BPs > 140/90 mm Hg, at least two documented BPs outside readings according to JNC 7 expert opinion guidelines the office < 140/90 mm Hg, and no evidence of target organ (Table 4) until there is greater consensus. damage.

The 2017 Guideline for the Prevention, Detection, Initial Evaluation of Newly Diagnosed Patients Evaluation and Management of High Blood Pressure in Adults by the American College of History. Once the diagnosis of hypertension is made, the (ACC)/American Heart Association (AHA) defines clinician should determine by history and physical hypertension as ≥ 130/80. However, Hypertension Canada’s examination whether the patient has evidence suggesting 2018 Guidelines for Diagnosis, Risk Assessment, , as well as other cardiovascular risk Prevention, and Treatment of Hypertension in Adults and factors. The history should focus on the following: Children and the 2018 European Society of Cardiology • Cardiovascular review of systems, including known (ESC) and European Society of Hypertension (ESH) Joint duration of hypertension Guidelines for the Management of Arterial Hypertension • Symptoms or previous personal/family history that helps continue to define HTN as ≥ 140/90 in the office. All to identify secondary hypertension guidelines stress the significance of BP ≥ 130/80 in those • Presence or absence of other cardiovascular risk factors with increased risk. • Psychosocial and environmental factors that may BP monitoring. BP can be monitored at home in two ways. influence BP control • Medications being taken • Home blood pressure monitoring (HBPM) – Patient or

caregiver records blood pressures at home with a blood pressure cuff. This requires knowledge and training in Physical examination. Based on expert opinion the JNC 7 proper technique. Upper arm BP cuffs are preferred, since recommendations for the physical examination of wrist and finger monitors are not reliable. Proper technique hypertensive patients are: and calibration of home BP cuffs should be verified in a • Two or more BP measurements separated by 2 minutes clinic setting if HBPM is to be utilized for clinical decision with the patient either supine or seated making. • Verification in the contralateral arm • Ambulatory blood pressure monitoring (ABPM) – • (BMI), calculated by weight (kg)/ 2 Automated cuff sent home from the clinic, worn for a pre- [height (m)] (possibly waist circumference) specified period of time (usually 24 hours). It is expensive, • Funduscopic examination for arteriolar narrowing, but is reliable and has been shown to be an independent nicking, hemorrhages, exudates, etc. predictor of cardiovascular morbidity and mortality when • Neck examination for carotid bruits, distended , or added to office based BP measures. enlarged thyroid • Heart/lung examination HBPM and ABPM identify patients whose BP at clinic visits • Abdominal examination for enlarged kidneys, masses, differs from BP outside the office. They may also be useful distended bladder, renal bruits, aortic in resistant hypertension. • Extremity examination for pedal pulses and edema • (WCH) refers to patients with • Neurological assessment, particularly for signs of elevated BP at office visits, but normal BP outside the cerebrovascular disease office. This condition is common (> 20% of patients with elevated BP) and may result in overtreatment if unrecognized. Both HBPM and ABPM can help identify

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Laboratory tests and diagnostic procedures. Essential hypertension. Consider the following tests Without ASCVD, ASCVD 10-year risk < 10%, and no before therapy is initiated. Screening for diabetes is CKD, treatment target is SBP < 140 mm Hg and DBP < 90 particularly important. mm Hg. ASCVD risk is based on the ACC/AHA pooled • Blood glucose • EKG • Potassium cohort ASCVD risk calculator.

• Creatinine • Hematocrit • Urinalysis With ASCVD, ASCVD 10-year risk ≥ 10%. Or CKD: • Calcium • Lipid panel - <130/80 mm Hg if without risk for hypotension (eg, Secondary and/or complicated hypertension. Consider without: , heart failure, older other testing and/or referral when secondary hypertension or age). complicated hypertension (does not respond to usual - Consider <140/90 mm Hg if risk for hypotension. measures, pre-existing controlled hypertension becomes uncontrolled, sudden onset of hypertension, and/or For CKD stages 3b-5, monitor more frequently due to malignant hypertension) is suspected. History and the above increased risk for hyperkalemia. laboratory screening may be helpful in detection. Age is an important factor in the ACC/AHA ASCVD risk Secondary hypertension and complicated hypertension calculator, resulting in a BP target of <130/80 mm Hg for etiologies include: most older adults. Even with normal values for blood • Chronic or acute pressure, , and a history of no smoking, men age ≥ 60 years and women age ≥ 70 years will have a calculated • Renovascular hypertension 10-year ASCVD risk ≥ 10%. Individualizing BP treatment • Sleep apnea goals is particularly important for older adults for whom • Medications or illicit drugs treatment to < 130/80 mm Hg may result in other clinical • Chronic kidney disease concerns (eg, hypotension and its risks). • Renovascular disease Diabetes is another important factor in the ACC/AHA • Primary aldosteronism ASCVD risk calculator, resulting in a BP target of < 130/80 • Coarctation of the aorta for most patients with diabetes. Having diabetes essentially • Chronic steroid therapy and Cushing’s syndrome doubles an individual’s risk that results from other factors. • Even with normal values for blood pressure, cholesterol, • Thyroid or parathyroid disease and a history of no smoking, with diabetes men age ≥ 55 years and women age ≥ 65 years will have a 10-year Medications and other reversible causes are described ASCVD risk > 10%. Many middle-age adults and some further in Table 5. younger adults with diabetes and with other risk factors for ASCVD will have a calculated 10-year ASCVD risk > 10%. Risk Stratification. The risk of in patients with hypertension is determined not only by the For patients at risk for hypotension (eg, orthostatic level of BP but also by the presence or absence of target hypotension, heart failure, older age), consider a treatment organ damage: target of SBP < 140 mm Hg and DBP < 90 mm Hg. The BP

Current diagnoses: Other risk factors: target is higher to avoid hypotension, which may result in • LVH • Smoking insufficient blood flow to organs (eg, kidneys in patients • CHF • (BMI ≥ 30 with CKD), dizziness, and fainting. The prevalence of • Angina kg/m2) orthostatic hypotension increases with age, from 4% for • Stroke or TIA • Physical inactivity individuals age 50-59 years to 19% for individuals over 80 • Chronic kidney disease • Dyslipidemia years. See the UMHS Heart Failure guideline for more (includes microalbuminu- • Diabetes detail on this topic. ria or proteinuria) • Estimated GFR < 60 • Peripheral arterial disease mL/min) Patients with CKD stages 3b-5 should be monitored more • Retinopathy • Age (> 55 for men, > 65 frequently for hyperkalemia. Commonly prescribed for women) hypertension medications (eg, angiotensin converting History of: enzyme inhibitors, angiotensin receptor blockers, • MI • Family history of premature cardiovascular potassium-sparing diuretics) may result in hyperkalemia in • CABG patients with decreased renal function. • CVA disease (men < 55 or women < 65) disease • TIA Clinical trial data reviewed by the Seventh Report of the Joint National Committee (JNC 7) support reducing SBP to Treatment of Hypertension < 140 mm Hg and DBP to < 90 mm Hg. This was confirmed by the panel members of the Eighth Joint National Treatment BP goal. The target BP depends on the presence Committee for ages 60 years and younger. For ages 60 years of other risk factors. and over, the latter recommended reducing SBP to < 150 mm 8 UMHS Hypertension Guideline, July 2019

Hg and DBP to < 90 mm Hg. The 2017 ACC/AHA precautions to avoid hypotension and to monitor for guidelines recommended reducing SBP to < 130 mm Hg and hyperkalemia. DBP to < 80 mm Hg, based on new data from SPRINT. Systolic blood pressure had not been evaluated as rigorously Treatment selection. While lifestyle modification is always as diastolic blood pressure until SPRINT looked at SBP recommended, the addition of medications depends on control and clinical outcomes. For patients with elevated disease severity and other risk factors. blood pressure and elevated ASCVD risk, aggressive treatment of HTN provides significant improvements in Patients with prehypertension but without risk factors or clinical outcomes. Current available data suggest that a SBP target organ damage (TOD) should have lifestyle target of < 130 mm Hg is reasonable. modification recommended.

Guidelines from outside the United States, including Patients with Stage 1 hypertension and no other risk factors Hypertension Canada 2018 Guidelines and the 2018 can be recommended for a trial of lifestyle modification for ESC/ESH Guidelines recommend target SBP of < 140 mm up to 12 months. With recent evidence suggesting that early Hg and DBP of < 90 mm Hg for adults without risk, and treatment to target blood pressure levels may attenuate the target SBP of < 130 mm Hg and DBP of < 80 mm Hg for expression of hypertension and improve clinical outcomes, adults with risk. more experts are recommending both medication and lifestyle modification initially, with plans to reduce or In all guidelines, accurate BP measurement using eliminate drug therapy as lifestyle goals are achieved. automated office BP or home BP measurement was recommended. A sustained decrease in SBP of 10 mm Hg Patients with Stage 2 hypertension or with either diabetes, or or DBP of 5-6 mm Hg for patients with hypertension any TOD should have drug therapy in addition to lifestyle decreases the risk of stroke by 35-40% and decreases the modification. Initial combination therapy with a thiazide plus chance of coronary heart disease by 20-25%. an additional agent is useful (or other combinations). Additionally, patients that are felt to have resistance to prior For patients with diabetes, goals for blood pressure treatment therapy or possibly less compliant may achieve better control have been evaluated in several randomized trials, particularly with initial combination therapy. ACCORD. SPRINT did not evaluate diabetic patients. For DBP, a target of 90 and likely 80 mm Hg provides marked Lifestyle modifications. Clinical trials have shown that benefits. Caution is suggested when DBP falls below 70 mm lifestyle modifications can lower BP. Lifestyle modifications Hg. Mortality increased when patients with diabetes had are best initiated and sustained through an educational DBP below 70. partnership between the patient and a multidisciplinary health care team. While team members may vary by clinical The American Diabetes Association’s 2019 Standards for setting, behavior-change strategies should include nutrition, Medical Care in Diabetes synthesize results from ACCORD exercise, and smoking cessation services. and SPRINT by focusing on diabetes as a risk factor for ASCVD. The ADA recommends that BP targets for patients Weight reduction and maintenance. Many individuals with diabetes be based on the patient’s ASCVD status and who are both overweight and hypertensive can lower their 10-year risk for ASCVD, consistent with the ACC/AHA BP with weight reduction. The effect is usually evident in the approach to setting BP targets based on ASCVD and early stages of weight loss and frequently occurs with only a ASCVD risk. The one difference is that for a BP target of < ten-pound reduction in weight. 130/80 mm HG, ACC/AHA set 10-year ASCVD risk level at ≥ 10% and the ADA set the level at ≥ 15%. This difference Modification of dietary sodium. The current is of little practical consequence. The effect of increasing age recommendation is to lower sodium intake to less than 2.4 on the calculation of ASCVD risk is sufficiently strong than grams per day. Encourage patients to lower their sodium anyone with an estimated 10-year risk that is > 10% and < intake by not adding salt to their food or in cooking; limiting 15% will have an estimated risk ≥ 15% within a couple of processed, convenience, or fast foods; and reading food years. Using 10-year ASCVD risk level of ≥ 10% initiates labels for sodium content. Water softeners contribute sodium lowering the goal to < 130/80 mm HG slightly earlier. to the water and may be significant.

For CKD, the “Kidney Disease: Improving Global Moderation of alcohol intake. Patients should not Outcomes” (KDIGO) group in 2012 recommended BP exceed a daily alcohol intake of 1 ounce of ethanol. This targets for patients with CKD of < 140/90 mm Hg if urine amount is contained in 2 ounces of 100 proof whiskey, 8 albumin excretion is < 30 mg per 24 hours and of < 130/80 ounces of wine, or 24 ounces of beer. mm Hg if albumin excretion is ≥ 30 mg per 24 hours. KDIGO is reviewing its recommendations based on the Adequate physical activity. Regular aerobic physical results of SPRINT, which included CKD patients. Based on activity may be beneficial for both prevention and treatment the results of SPRINT, our recommendation is also to apply of hypertension. It may enable weight loss, improve the target of 130/80 mm Hg to CKD patients with urine functional health status, and diminish mortality and risk for albumin excretion < 30 mg per 24 hours. We add practical 9 UMHS Hypertension Guideline, July 2019 cardiovascular disease. Thirty to forty-five minutes of brisk physiological action is indicated. Combining medications walking three or four times weekly is adequate and effective. from the same class is not effective. Table 2 shows costs of Resistive isotonic activities as sole exercise are not drug treatment for various antihypertensive agents. recommended to lower BP in hypertensive patients. Diuretics, beta blockers, ACE inhibitors, and long-acting Tobacco avoidance. All smokers should be offered dihydropyridine CCBs have been shown in randomized assistance in smoking cessation and strongly advised to quit. controlled trials to reduce cardiovascular morbidity and mortality. The ALLHAT study was a large multicenter direct Potassium. High dietary potassium may protect against comparison RCT designed to determine if the older or newer hypertension development. Hypokalemia may exacerbate agents are more effective in prevention of cardiovascular hypertension and induce ventricular arrhythmia. Potassium morbidity and mortality. It compared treatment starting with sparing diuretics and ACE inhibitors retain potassium and a thiazide diuretic, an ACE inhibitor, a long-acting magnesium whereas simple potassium chloride replacement dihydropyridine CCB, and an alpha-blocker. Beta blockers does not replace magnesium. and centrally-acting agents were used as the second step drugs; almost three-fourths of patients required two or more Other dietary factors. Calcium supplementation may drugs. Beta blockers were the most commonly used second result in a very small reduction in BP (systolic -1.27 mm Hg; agent. The alpha blocker arm was discontinued early because diastolic -0.24 mm Hg). No definitive data suggest of an excess of adverse outcomes. The other agents magnesium supplementation lowers blood pressure. Dietary performed equally in primary outcome (coronary endpoints), have no effect on blood pressure. Acute caffeine but the thiazide (chlorthalidone), in moderate to high doses, ingestion may elevate BP; however, tachyphylaxis to chronic was superior in secondary outcomes (stroke and CHF). This ingestion attenuates this effect. A diet low in sodium and finding was consistent across age and race, and in all saturated fats, and high in vegetables, fruits, and low dairy subgroups including patients with diabetes, coronary disease, products has been shown to lower blood pressures (the and hyperlipidemia. “DASH” diet). Existence of other risk factors, co-morbidities, and concern Drug therapy. Hypertension is a chronic disease. Thus, the for untoward drug effects may influence initial drug choice of which medication(s) to prescribe has long term selection. ACE inhibitors, ARB’s, and CCBs may be initial implications. options. Beta blockers are not preferred as initial therapy in the elderly unless compelling other conditions exist, eg, Drug selection. Data from a very large multicenter RCT coronary artery disease (see Table 1). Recent meta-analyses supported by smaller studies demonstrate that moderate-to- suggest that beta blockers may be less effective in stroke high dose thiazide diuretics (chlorthalidone 25 mg/day) are reduction when compared to other classes of as good as any other class of agents in reducing antihypertensive therapy. Beta blocker usage for HTN may cardiovascular adverse outcomes, and superior in secondary be deferred unless CAD or CHF exists. outcomes such as stroke and CHF. Most patients will require two or more drugs to achieve control, and a few will not For without DM or CKD, a thiazide tolerate thiazides. The choice of additional or alternative diuretic and/or CCB may be considered as first and second medication should be individualized to achieve the target BP line antihypertensive medications. However, an ACEI or and the following goals: ARB may be more appropriate for African Americans with  Once daily administration DM and/or CKD with estimated GFR of < 60 ml/min and  Reduction in CV complications demonstrated in clinical also for those where a clinical suspicion of milder CKD trials exists, eg, positive for microalbuminuria. This  Choice of agent(s) that also treat concurrent conditions recommendation differs from JNC 8, which recommends a  Least potential disruptive side-effects based on thiazide diuretic or CCB as initial antihypertensive therapy concurrent conditions or lifestyles for African Americans, including for those with diabetes.  Least expensive (both in pharmaceutical and laboratory monitoring costs) No clear guidelines exist regarding whether specific drug  Fixed combination therapy can be more cost-effective combinations impart superior clinical outcomes (eg, and may improve compliance. Some patients may benefit ACEI/CCB vs. ACEI/diuretic. Large, well-designed trials from beginning with fixed combination therapy (eg, in (ACCOMPLISH with benazepril/amlodipine vs. Stage 2 hypertension or for patients resistant to benazepril/HCTZ, ACCELERATE with aliskiren and monotherapy in the past). amlodipine vs. either alone) raise the possibility that a combination of a blocker of the renin-angiotensin system and All agents within a class have similar physiological action, calcium channel blocker may be superior to other except calcium channel blockers and beta blockers, which combinations and single agents. Currently, the combinations have sub-classes with different physiological effects. If of ACEI/ARB, ACEI/direct renin inhibitor (DRI), or monotherapy is not effective in reaching the BP goal, the ARB/DRI are not recommended in HTN management. addition or substitution of a different class with different

10 UMHS Hypertension Guideline, July 2019

Diuretics. Thiazide diuretics have traditionally been the this class induce cough equally, which may be disabling initial treatment for most patients with hypertension. enough with some patients to result in the need to discontinue Although the trials that showed a decrease in cardiovascular the drug; cough occurs more often in women. This class is morbidity and mortality used moderate to high dose diuretics, contraindicated in pregnancy. higher dosages of thiazide diuretics have shown only minimal improvement in BP control. Consequently, the Angiotensin II receptor antagonists (ARB) displace maximum suggested dosage of thiazide diuretics has been angiotensin II (AII) from its type 1 receptors. Losartan and lowered in order to avoid metabolic side-effects. The range irbesartan have been shown in randomized, double-blind of hydrochlorothiazide is 12.5 mg to 50 mg each morning. In trials in diabetics with microalbuminuria or azotemia to patients more vulnerable to side effects, such as the elderly, decrease the development of frank proteinuria or progression even this range should be approached with caution. The most to renal failure requiring dialysis or transplantation. In studied thiazide is chlorthalidone, though patients who have systolic heart failure and are intolerant to hydrochlorothiazide is the predominant prescription thiazide an ACEI because of cough, ARBs are recommended. in the USA. Side effects. Angioedema has been rarely reported with Side effects. Thiazide diuretics increase the frequency of Losartan, but has occurred in patients with prior angioedema sexual dysfunction in men and women and initially may on ACE inhibitors. Losartan has a uricosuric effect (i.e. cause interruptions in daily routine for micturition. Thiazides increases excretion of uric acid, lowering concentration in cause a short-term increase in LDL cholesterol; however, blood) that is unique compared to others in this class. long-term trials have shown minimal change and outcome Losartan may be less efficacious compared to others in this studies show no clinical impact. Thiazides slightly increase group at lowering BP and should be used twice a day. This the risk for diabetes (ALLHAT). While small changes in class is contraindicated in pregnancy. LDL and glycemic control are not contraindications, the clinical impact of these metabolic aberrations has yet to be Calcium channel blocking (CCB) agents. There are elucidated. Thiazides can increase uric acid and precipitate three classes of calcium channel blocking agents based on attacks of gout. Hypokalemia is uncommon at usual (12.5-25 different calcium channel receptors, all with different mg) doses but occurs relatively often at doses of 50 mg or physiological effects and side effects: verapamil, diltiazem, more. and dihydropyridines. All long acting dihydropyridine CCBs have been shown to reduce blood pressure and Loop diuretics. These diuretics are preferred for cardiovascular events. individuals with renal impairment (serum creatinine ≥ 2.5 mg/dl) and individuals allergic to thiazide diuretics. Loop Of the dihydropyridine CCBs, the longer-acting agents (eg diuretics are useful for reducing preload, which contributes amlodipine, felodipine, nisoldipine) make single daily to hypertension in renal-impaired individuals. Hypokalemia dosing possible. These drugs provide the most reliable and is less common due to the renal impairment, but should still significant blood pressure reduction in most patient subtypes. be monitored. Loop diuretics are not as likely as thiazide They are particularly effective in stroke reduction and have diuretics to cause gout. been shown to reduce overall CVD risk. The short-acting agents are not indicated for hypertension. Angiotensin converting enzyme (ACE) inhibitors. As a class, ACE-inhibitors have similar actions and side effects, Some effects with specific diseases include: with the only major difference being duration of action. ACE • Acute coronary syndrome. Short-acting dihydropyridines inhibitors reduce BP with generally few side effects and slow should be avoided in the first 24-48 hours of an acute the decline of renal function in most diseases. The coronary syndrome. renoprotective effect may be augmented when combined with angiotensin receptor blocker. Ramipril was shown in a • Chronic kidney disease. Dihydropyridines should be randomized controlled trial to decrease cardiovascular events avoided as a single agent for patients with in hypertensive and normotensive individuals with systolic microalbuminuria or proteinuria, as they will worsen heart failure over placebo. However, newer trials have not protein loss and renal function, but may be used in shown renin-angiotensin blockade to be superior to other combination with ARB or ACE inhibitors. medications in decreasing morbidity and mortality. Onset of • Chronic CAD. Verapamil has shown to be as effective as diabetes was not prevented by ramipril in a study directly a beta-blocker in patients with CAD or remote history of addressing this issue. MI. The long-acting dihydropyridine agents may be used in patients with angina; however, some feel that they only Side effects. Angioedema is a rare side effect (0.1-0.7%), should be used when combined with a beta blocker. All which may be life-threatening and may occur at any point in CCBs can be used in hypertensive patients with chronic the treatment. The incidence may be higher in African CAD to reduce anginal episodes. Americans. Although per se is not a  Aortic regurgitation. Nifedipine may be useful in contraindication for ACE therapy, renal impairment may hypertensive patients with aortic regurgitation. occur in patients with bilateral renal artery stenosis or unilateral renal artery stenosis with a single kidney. All in 11 UMHS Hypertension Guideline, July 2019

Side effects. Edema may occur and is more pronounced unknown. Aliskiren should be used as a fourth line agent in with the dihydropyridine agents. patients who have failed standard therapy.

Bradycardia is a side effect of verapamil and diltiazem, but Side Effects. As with other RAAS agents, aliskiren can renders them useful agents in the treatment of atrial cause an increase in serum creatinine and potassium fibrillation/SVT). Verapamil has more pronounced especially is used in combination with an ACE inhibitor or bradycardia effects and often results in constipation. ARB. This class is contraindicated in pregnancy. Verapamil and diltiazem may increase risk for statin myopathy (cytochrome 3A4 inhibition). Peripheral alpha blockers. Alpha blockers should not be used as initial therapy for hypertension but may be Aldosterone inhibitors. Spironolactone and eplerenone added to a thiazide or other outcome-improving agent for are used in certain conditions associated with hypertension, additional BP control, or when treatment for lower such as resistant hypertension, hyperaldosteronism, and urinary tract symptoms due to prostatic hyperplasia is potassium wasting. However, when used in patients with desired. chronic kidney disease, or concurrently with potassium sparing agents (ACEI, ARB, triamterene), they carry Side effects: Alpha blockers may cause first dose significant risk for life-threatening hyperkalemia. syncope, so are generally started at bedtime and slowly Combination therapy is generally restricted to patients with titrated up in dose. They may cause fluid retention and systolic heart failure, and requires close follow-up. edema. The ALLHAT study showed a 25% increase in Gynecomastia and breast pain are common side effects with cardiac events in the doxazosin vs. chlorthalidone group. spironolactone, causing discontinuation in about 10%. Centrally-acting alpha-2 agonists are less often used due Beta blockers have been shown to reduce cardiovascular to their side-effects. They have no evidence of outcome morbidity and mortality in controlled clinical trials for both benefit. Methyldopa remains a first line agent in pregnancy. diastolic and isolated . However, one study showed that diuretics are superior to beta-blockers for Side effects. May induce bradycardia; dry mouth and stroke reduction, and another showed that losartan is superior sedation are common. Rebound hypertension may occur with to beta blocker for CVD reduction. The results of three meta sudden discontinuation of clonidine. analyses suggest that other antihypertensive agents are superior to most beta-blockers for initial therapy. In addition, Direct vasodilators. These drugs are fourth line agents atenolol has poorer outcomes when compared to other beta- for essential hypertension and should be used in patients who blockers (an excess stroke risk of 17%). have failed standard therapy. Direct vasodilators induce reflex tachycardia and thus should be combined with a beta Beta blockers are indicated for patients with coronary disease blocker or non-dihydropyridine calcium channel blocker. or CHF unless specific contraindications or documented Due to increased fluid retention, they should also be intolerance exists. Certain beta blockers (eg, carvedilol) also combined with a diuretic. These agents have not been shown have alpha blocking properties and are useful for to reduce left ventricular hypertrophy. They are third- or maintenance therapy of heart failure. Discussion regarding fourth-line agents, sometimes useful in refractory other properties of beta blockers, such as B1 selectivity and hypertension. lipid solubility, are beyond the scope of this guideline. Hydralazine may produce a lupus erythematosus-like While a target of < 60/minute has been suggested syndrome; the syndrome is extremely rare when the daily in using beta blockers for patients with systolic heart failure, dose is less than 200 mg. Side effects include headache, no target has been established for patients with palpitations, anorexia, and nausea. At least twice daily uncomplicated hypertension. dosing requirements limit the usefulness of this drug. Hydralazine has shown benefit in CHF when combined with Side effects. Occasionally fatigue and uncommonly a nitrate. impotence are side effects at the recommended low doses. Beta-1 blockers produce the same dramatic reduction in Minoxidil is effective in treating the severest forms of angiotensin II levels as ACE inhibitors, and the two agents hypertension, although it is used less frequently today together have an additive effect. Though beta blockers may because ACE inhibitors and calcium channel blockers may raise triglycerides and lower HDL cholesterol, these effects be as effective. Side effects include hypertrichosis and fluid have not been found to be clinically significant in outcome accumulation in serous cavities, including the pericardium. studies. Monitoring Blood Pressure Control Renin inhibitors are a novel way of blocking the renin- angiotensin-aldosterone system (RAAS). The first drug in No studies demonstrate the most appropriate monitoring of this class is aliskiren. The drug has been shown to lower BP and follow-up. The following is a consensus opinion of blood pressure alone or in combination with other antihypertensives, but its effects on clinical outcomes is 12 UMHS Hypertension Guideline, July 2019 the guideline team. If blood pressure is uncontrolled after persistent attempts to do so, or multiple (> 3) drugs are needed, consider referral to Blood pressure measurement. All patients who have been a hypertension specialist. diagnosed with hypertension should be taught the technique of home BP monitoring, assuming that there are no cognitive Intolerance to multiple medications may be an indication of deficiencies that would preclude the technique. A handout over-treated hypertension due to a significant white coat about the purchase and proper technique may be used. effect. Ambulatory or home BP monitoring may then be Patients should purchase an electronic, digital home BP cuff. helpful. The proper cuff size should be indicated to the patient by the healthcare provider. Automatic (self-inflating) and non- Controlled BP. Once BP is controlled, office visits every 3- automatic electronic monitors are equally effective, with the 6 months are appropriate. At any time, for any stage of non-automatic being cheaper but more labor intensive. hypertension, consultation with a clinician skilled in the management of hypertension should be considered if BP Patients should be instructed to take their BP daily, upon cannot be controlled adequately, patient compliance is poor, awakening and before dinner (other times as necessary), until or there is difficulty identifying exacerbating conditions or the BP is controlled to the targeted range discussed above. medications. After BP control is achieved, BP may be obtained monthly. The BP readings should be recorded on a BP monitoring Resistant hypertension. Resistant hypertension is the sheet and sent or brought to the physician. The wrist and failure to reach goal BP in patients who are adhering to full finger units, although easy to use, are not reliable for doses of an appropriate 3-drug regimen that includes a monitoring blood pressure. diuretic. After excluding potential identifiable causes of hypertension (Table 5), clinicians should explore reasons Prehypertension. Follow at least annually. why the patient is not at the goal BP. Particular attention should be paid to diuretic type and dose in relationship to Stage 1 hypertension. Once antihypertensive therapy is renal function because thiazide-type diuretics lose effect initiated, most patients should return for follow-up and once the GFR falls < 30 ml/min. Consultation with a adjustment of medications at monthly intervals or less until hypertension specialist should be considered if goal BP the BP goal is reached. The effect of an antihypertensive cannot be achieved. agent on BP is typically stabilized in < 2 weeks. At each visit, BP control, adverse medication effects, patient adherence, and new target organ damage should be assessed. If after 1- Special Considerations 3 months the BP does not reach the targeted goal: 1) Ensure that the patient is believed to be taking the Hypertension and Pregnancy. The use of antihypertensives medication as prescribed. in pregnancy must consider fetal well-being. Treating 2) Ensure that the dose of the medication is adequate. uncomplicated Stage 1 hypertension is often not necessary in 3) Reconsider reversible causes. otherwise low-risk women with normal renal function and no 4) Add a second drug from another class if necessary to other target organ disease. These women should be closely reach goal. followed during pregnancy. Pre-eclampsia or other pregnancy-induced hypertension should be treated by a After BP is at goal and stable, follow-up visits can usually be physician experienced in managing these diseases. at 3- to 6-month intervals. A randomized controlled trial showed that for stable patients that patient outcomes were Women considering pregnancy, who are hypertensive and equivalent for follow-up intervals of 3 and 6 months. No require treatment, should be on antihypertensive medication evidence currently exists regarding the equivalence of 6- ideally three to six months prior to conception. Medications month and 12-month intervals. Serum potassium and for treating significant hypertension during pregnancy, in creatinine should be monitored at least annually. Monitoring order of preference, are: for microalbuminuria may also be useful. 1) Methyldopa – the drug with the longest experience Stage 2 hypertension. Follow-up is generally similar to that Problems with this medication include frequent side for medical therapy for Stage 1 hypertension, except more effects and the need to dose multiple times a day. frequent visits may be necessary, eg, more frequently than 2) Beta-blocker with or without diuretic (avoiding atenolol, monthly intervals initially to adequately control BP. which may be associated with intrauterine growth retardation) – are relatively popular and the first choice Additional considerations. Most patients will require two of some. or more medications to reach goal. Fixed dosage 3) Labetalol combination antihypertensive medications may simplify 4) Calcium channel blockers therapy and improve adherence, but generic individual agents are usually less costly. Diuretics are also acceptable to use.

Contraindicated in pregnancy are ACE inhibitors, ARBs, and 13 UMHS Hypertension Guideline, July 2019 renin inhibitors. angiotensin II receptor antagonist, beta blockers (selective and non-selective), calcium channel blockers Ongoing diabetes screening. While screening for diabetes (dihydropyridine and non- dihydropyridine forms), centrally is recommended when a mean BP > 135/80 is first identified, acting alpha-2 agonist, diuretics (thiazide and non-thiazide, for patients with hypertension an optimal interval for loop, potassium-sparing), vasodilator (direct), avoidance subsequent screening for diabetes is not known. The (alcohol, stress, tobacco), blood pressure monitoring American Diabetes Association (based on expert opinion) (ambulatory, home), dietary (caffeine, calcium, garlic, recommends screening at 3-year intervals. magnesium, onion, potassium, sodium), exercise, disease- based management (stroke, coronary artery disease, Elderly patients. The benefit of treating hypertension in cardiac, heart failure, arterial fibrillation, peripheral older adults has been well established. The HYVET study , diabetes, chronic kidney disease, confirmed substantial reduction in cardiovascular risk and ), and resistant hypertension.. Detailed mortality from treating hypertension in patients age 80 and search terms and strategy available upon request. older, to a target of 150/80 mm Hg. In 2013 the full literature search was deferred while waiting No clear benefit has been shown for SBP targets lower than for the search results of JNC 2013 (“JNC 8”). However, < 150 (eg, < 140). Lowering DBP to < 65 is a theoretical risk. expert member of the team identified three topics for which No clear evidence exists to determine the relative risk of important new evidence had been published and systematic achieving a SBP < 150 if that treatment also lowers DBP to searches were performed on those topics. The search was <65. conducted on Medline prospectively using the major keywords of: hypertension, human adults, English language, Orthostasis is a common problem in the elderly and guidelines, clinical trials, cohort studies, and published from monitoring standing and supine BP is important during 1/1/03 through 6/1/13. Terms used for specific topic searches treatment to identify this. within the major key words included: combination of ‘ACE (angiotensin converting enzyme) inhibitors and ARB Antihypertensive choice in the elderly is similar to other age (angiotensin receptor blockers), combination of ARB and groups. Beta blockade should be avoided unless there is a DRI (direct renin inhibitors), and patients age ≥ 65 years compelling indication such as CAD or CHF. Lower initial (older/elderly) and target blood pressure and treatment. antihypertensive drug doses and slower titration is generally recommended. The search was conducted in components each keyed to a specific causal link in a formal problem structure (available upon request). The search was supplemented with very Related National Guidelines recent information available to expert members of the panel, including abstracts from recent meetings and results of This guideline is consistent with JNC 7, updated with results clinical trials. Negative trials were specifically sought. The of major trials subsequently (see references). It is consistent search was a single cycle. Conclusions were based on with the report from the panel members appointed to JNC 8, prospective randomized clinical trials if available, to the except for African Americans without evidence diabetes or exclusion of other data; if randomized controlled trials were CKD, this guideline recommends the same initial drugs as not available, observational studies were admitted to for other patients without evidence of diabetes or CKD. consideration. If no such data were available for a given link in the problem formulation, expert opinion was used to estimate effect size.

Strategy for Literature Search Measures of Clinical Performance Preliminary evidence was identified using literature considered relevant in JNC 7 (see annotated references). National programs with related clinical performance That report utilized literature searches of the preceding measures include the following: reports and added a systematic search of literature from  Centers for Medicare & Medicaid Services (CMS) January 1997 through April 2003. Regional programs that have clinical performance measures In 2007 a search of literature from 2003–2007 was of prenatal care include the following. performed that was also utilized to develop the 2009 version  Blue Cross Blue Shield of Michigan (BCBSM) of this guideline. That search was conducted on Medline  Blue Care Network [HMO]: clinical performance prospectively using the major keywords of: hypertension, measures (BCN) human adults, English language, clinical trials, guidelines, and published from 1/1/03 through 5/1/07. Terms used for These program’s clinical performance measures for specific topic searches within the major key words included: hypertension are summarized below. When programs have alpha 1 blocker, angiotensin converting enzyme inhibitors, measures, the measures are generally similar, although 14 UMHS Hypertension Guideline, July 2019 specific details vary (eg, population inclusions and Committee of the University of Michigan Faculty Group exclusions). Practice and the Executive Committee for Clinical Affairs of the University of Michigan Hospitals and Health Centers. Controlling high blood pressure. The percentage of patients aged 18–85 years with a diagnosis of hypertension and whose blood pressure was adequately controlled (< 140/90) Acknowledgements (Medicare, BCBSM, BCN). The following individuals are acknowledged for their Hypertension improvement. Improvement in blood pressure. contributions to previous versions of this guideline. The percentage of patients aged 18-85 years with a diagnosis of hypertension whose blood pressure improved during the 1997: Steven Yarows, MD, FACP; William Barrie, MD; measurement period (Medicare). Christine Birmingham, RN; Steven Erickson, PharmD; Kenneth Jamerson, MD; Christopher Wise, PhD; Philip Preventive care and screening for hypertension. Screening Zazove, MD. for high blood pressure and follow-up documented. Percentage of patients aged 18 years and older seen during 2003: William Barrie, MD; Janice Stumpf, PharmD; the reporting period who were screened for high blood Kenneth Jamerson, MD; Philip Zazove, MD; Lee Green, pressure AND a recommended follow-up plan is MD (consultant). documented based on the current blood pressure reading (Medicare). 2009: Masahito Jimbo, MD; William E. Barrie, MD; Michael P Dorsch, PharmD; R Van Harrison, PhD; Additional measures regarding care for hypertension exist Kenneth A. Jamerson, MD. for patients with specific medical conditions, eg, diabetes, coronary artery disease. 2014: Masahito Jimbo, MD; Michael P Dorsch, PharmD; Mark W Ealovega, MD, R. Van Harrison, PhD; Kenneth A. Jamerson, MD. Disclosures

University of Michigan Health System endorses the References Guidelines of the Association of American Medical Colleges and the Standards of the Accreditation Council for The ACCORD Study Group. Effects of intensive blood- Continuing Medical Education that the individuals who pressure control in mellitus. NEJM, 2010; present educational activities disclose significant 362: 1575-1585. relationships with commercial companies whose products or services are discussed. Disclosure of a relationship is not The ALLHAT Officers and Coordinators for the ALLHAT intended to suggest bias in the information presented, but is Collaborative Research Group. Major Outcomes in High made to provide readers with information that might be of Risk Hypertensive Patients Randomized to Angiotensin- potential importance to their evaluation of the information. Converting Enzyme Inhibitor or calcium Blocker vs Diuretic: The Antihypertensive and Lipid-Lowering Team Member Relationship Company Treatment to Prevent Heart Attack Trail (ALLHAT). JAMA 288:2981-2997, 2002. Michael P. Dorsch, Speaker’s Astra Zeneca, PharmD Bureau Boehringer American Diabetes Association. Standards of medical care Ingelheim, for diabetes – 2010. Diabetes Care, 2019; 42 Supplement 1: Jansen S1-S193. Mark W. Ealovega, MD (none) R. Van Harrison, PhD (none) Aronow WS, Fleg JL, Pepine CJ, et al. ACCF/AHA 2011 Kenneth Jamerson, MD (none) expert consensus document on hypertension in the elderly. Masahito Jimbo, MD (none) Journal of the American College of Cardiology, 2011; 57(20): 2037-2114.

Review and Endorsement Beckett NS, Peters R, Fletcher AE, et al. Treatment of hypertension in patients 80 years of age or older. (HYVET Drafts of this guideline were reviewed in clinical study.) NEJM, 2008; 358: 1887-1898. conferences and by distribution for comment within departments and divisions of the University of Michigan Brown MJ, McInnes GT, Papst CC, Zhang J, MacDonald Medical School to which the content is most relevant: TM. Aliskiren and the calcium channel blocker amlodipine Family Medicine, General Medicine, and Cardiology. The combination as an initial treatment strategy for hypertension final version was endorsed by the Clinical Practice 15 UMHS Hypertension Guideline, July 2019 control (ACCELERATE): a randomised, parallel-group trial. Lancet 2011; 377: 312-320. ONTARGET Investigators, Yusuf S, Teo KK, Pogue J, Dyal L, Copland I, Schumacher H, Dagenais G, Sleight P, Denardo SJ, Gong Y, Nichols WW, et al. Blood pressure and Anderson C. Telmisartan, ramipril, or both in patients at high outcomes in very old hypertensive coronary artery disease risk for vascular events. N Engl J Med. 2008 Apr patients: An INVEST substudy. American Journal of 10;358(15):1547-59. Medicine, 2010; 123(8):719-726. Parving HH, Brenner BM, McMurray JJ, de Zeeuw D, Hansson L. Lindholm LH. Ekbom T. Dahlof B. Lanke J. Haffner SM, Solomon SD, Chaturvedi N, Persson F, Desai Schersten B. Wester PO. Hedner T. de Faire U. Randomised AS, Nicolaides M, Richard A, Xiang Z, Brunel P, Pfeffer trial of old and new antihypertensive drugs in elderly MA; ALTITUDE Investigators. Cardiorenal end points in a patients: cardiovascular mortality and morbidity the Swedish trial of aliskiren for type 2 diabetes. N Engl J Med. 2012 Dec Trial in Old Patients with Hypertension-2 study, Lancet. 6;367(23):2204-13. 354(9192):1751-6, 1999 Nov 20. Pfeffer MA, Swedberg CB, Held P, et al. Effects of Hansson L. Zanchetti A. Carruthers SG. Dahlof B. Elmfeldt candesartan on mortality and morbidity in patient with D. Julius S. Menard J. Rahn KH. Wedel H. Westerling S. chronic heart failure: the CHARM-Overall programme. Effects of intensive blood-pressure lowering and low-dose Lancet 2003; 362:759. aspirin in patients with hypertension: principal results of the Hypertension Optimal Treatment (HOT) randomized trial. Podymow T, August P. Update on the use of HOT Study Group, Lancet. 351(9118):1755-62, 1998 Jun antihypertensive drugs in pregnancy. Hypertension 13. 2008;51:960-969.

The Heart Outcomes Prevention Evaluation Study The 7th report of the Joint National Committee on Investigators. Effects of an angiotensin-converting–enzyme Prevention, Detection, Evaluation, and Treatment of High inhibitor, Ramipril, on cardiovascular events in high-risk Blood Pressure. Hypertension, 2003; 42:1206. Complete patients, N Engl J Med 2000; 342:145-153, Jan 20, 2000. report: NHLBI, 2004, NIH Publication No 04-5230.

Jamerson K, Weber MA, Bakris GL et al for the The SPRINT Research Group. A randomized trial of ACCOMPLISH Trial Investigators. Benazepril plus intensive versus standard blood-pressure control. N Engl J amlodipine or hydrochlorothiazide for hypertension in high- Med. 2015; 373:2103–2116. risk patients. NEJM, 2008; 359: 2417-2428. Whelton PK, Carey RM, Aronow WS, et al. 2017 James PA, Oparil S, Carter BL, et al. 2014 evidence-based ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/N guideline for the management of high blood pressure in MA/PCNA Guideline for the Prevention, Detection, adults: Report from the panel members appointed to the eight Evaluation, and Management of High Blood Pressure in Joint National Committee (JNC 8). JAMA, doi: Adults: Executive Summary: A Report of the American 10.1001/jama.2013.284427. Published online Dec. 18, 2013. College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. Hypertension. 2018 Kidney Disease: Improving Global Outcomes (KDIGO) Jun;71(6):1269-1324. doi: 10.1161/HYP.0000000000000066. Blood Pressure Work Group. KDIGO Clinical Practice Epub 2017 Nov 13. Review. No abstract available. Erratum Guideline for the Management of Blood Pressure in Chronic in: Hypertension. 2018 Jun;71(6):e136-e139. Hypertension. Kidney Disease. Kidney International, Supplement. 2012; 2: 2018 Sep;72(3):e33. PMID: 29133354 337–414. Williams B, Mancia G, Spiering W, et al. 2018 Practice Lasagna L. Diuretics vs alpha-blockers for treatment of guidelines for the management of arterial hypertension of the hypertension: lessons from ALLHAT. Antihypertensive and European Society of Hypertension (ESH) and the European Lipid-Lowering Treatment to Prevent Heart Attack Trial, Society of Cardiology (ESC). Blood Press. 2018 JAMA. 283(15):2013-4, 2000 Apr 19. Dec;27(6):314-340. doi: 10.1080/08037051.2018.1527177. Erratum in: Blood Press. 2019 Jan 9;:1. PMID: 30380928 Lindholm LH, Carlberg B, Samuelsson O. Should [beta] blockers remain first choice in the treatment of primary hypertension? A meta-analysis. The Lancet, 2005; 366 (9496):1545-1552.

Nerenberg KA, Zarnke KB, Leung AA, et al. Hypertension Canada's 2018 Guidelines for Diagnosis, Risk Assessment, Prevention, and Treatment of Hypertension in Adults and Children. Can J Cardiol. 2018 May;34(5):506-525. doi: 10.1016/j.cjca.2018.02.022. Epub 2018 Mar 1. 16 UMHS Hypertension Guideline, July 2019

APPENDIX. Standardized Blood Pressure Measurement

Types of Measuring Devices • Aneroid manometer could be used. However, the deflated cuff should read exactly zero, and it should be calibrated at least yearly, unless used frequently and then yearly. • Electronic manometers should be calibrated twice a year if used weekly, or once a year if used less often. • The cuff should be the appropriate size for the measured arm, and each cuff should have markers to note the proper selection. Proper Technique 1. Prior activity. Ideally, the patient should not have:  within 30 minutes – smoked, ingested caffeine, or exercised  within 2 hours – eaten or ingested alcohol 2. Preparation. The patient should sit with their back supported and feet on the floor (not seated on the exam table) for 5 minutes before the 1st blood pressure is taken. 3. First visit: bilateral measures. The blood pressure should be measured at least once in each arm (at the patient’s first visit) to assure that there is no difference in blood flow (i.e., should be < 10 mm Hg difference), and if there is a significant difference, the higher pressure should be used thereafter. 4. Cuff. Improper cuff size is the most common source of measurement error. The arm should be bare, and the cuff should be fitted securely so that the bladder midline is over the brachial artery and the lower edge of the cuff is 1 inch above the antecubital fossa. 5. Gauge. The gauge should be at eye level. 6. Arm. The patient’s arm should be supported, and the stethoscope or measurement point should be at heart level. 7. Inflation. Inflate the cuff at least 30 mm Hg above the systolic reading and deflate at a maximum of 2-3 mm per second or a maximum of 2 mm per pulse beat between the Korotkoff sounds. 8. Measurement. Record the systolic reading at the first sound heard Korotkoff phase I and the diastolic reading as the last sound heard Korotkoff phase V. If there is a muffling of the sound, this should also be recorded Korotkoff phase IV (eg - 150/50/0). 9. Repeated measurement. Take the patient’s pulse while waiting to repeat a second measurement after 1-2 minutes. If the measurement is performed immediately after walking into the room and the reading is normal, it should be recorded and repeated in 1-2 minutes. If the blood pressure is elevated immediately after walking into the room, it should not be recorded and the blood pressure should be repeated after 5 minutes of rest. At least two readings should be taken, and if the readings vary by more than 5 mm Hg diastolic, the readings should be repeated until there is less variability. 10. Other recorded information. The arm used, position of the patient, and the size of the cuff (when non-standard cuff size used) should be recorded. 11. Inform. Inform the patient of the readings.

17 UMHS Hypertension Guideline, July 2019